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Re: To E or Not to E?

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Thank you very much for this post. This is a little bit off-topic,

but I use a tocotrienol formulation (Twin Lab Rice Bran

Tocotrienols) therapeutically for my 3-year-old, who has a rare

neurological disease called Familial Dysautonomia. A lab at Fordham

found that gamma and delta tocotrienol increase production of a

protein called IKAP that is in short supply in my son's body due to

his disease, which is a genetic mutation that results in his cells

producing a mutated/truncated form of the protein, with an adverse

impact on his autonomic nervous system. This supplement keeps my son

out of life-threatening autonomic crises (along with another

supplement found by the same lab to actually cause the cells to not

truncate the protein; this other supplement is EGCG, and enzyme from

green tea). I have been ingesting the " empty " tocotrienol capsules

after squeezing them into his liquified food (he is tube-fed; I use

a Vita-mix to make his food), just thinking (gut feeling) it can't

hurt me and might help. Now I see from your post that this compound

may be protective against breast cancer. I have an increased risk

because of an Ashkenazi Jewish background. I now think I will begin

taking the tocotrienol myself, not just the empty capsule.

--- In , " old542000 " <apater@m...>

wrote:

> Hi All,

>

> To " E " or Not to " E? Is that the question?

> The below paper seems to suggest that

> we should " E " ?

>

> The PDF is available for the below.

>

> It is not yet in Medline, but the author writes

>

> many " Abstract not available " NEWS AND ANALYSIS

> papers.

>

> Cheers, Al Pater.

>

> NEWS AND ANALYSIS

> Medical News & Perspectives

> To " E " or Not to " E, " Vitamin E's Role in Health and Disease Is

> the Question

> M.J. Friedrich

> JAMA. 2004;292:671-673.

> BOSTON—From the pharmacy shelf to

> the kitchen shelf, vitamin E has be-come

> a common presence—not sur-prising

> for a substance touted as some-thing

> that can help prevent and treat

> maladies ranging from cardiovascular

> disease to cancer. A good deal of labo-ratory

> data and results from epidemio-logical

> and retrospective studies sup-port

> the notion that vitamin E can help

> ward off myocardial infarctions and

> keep cancer at bay.

> Findings from a variety of random-ized

> controlled trials, however, have

> failed to show consistent health ben-efits

> and many questions remain un-answered

> about this micronutrient. But

> don't chuck the bottle of vitamin E into

> the trash bin yet. A group of leading vi-tamin

> E researchers gathered here in

> May for a conference on Vitamin E and

> Health sponsored by the New York

> Academy of Sciences reviewed evi-dence

> of the role this vitamin plays in

> human health and disease and dis-cussed

> new information that recently

> has begun to emerge.

> Vitamin E is known primarily as an

> antioxidant that helps rid the body of

> damaging free radicals, which can

> wreak havoc on cells and DNA by in-creasing

> the oxidative stress associ-ated

> with many diseases. But the

> vitamin also appears to perform nonan-tioxidant

> functions that may benefit

> health by exerting anti-inflammatory

> actions and anticoagulant effects and by

> regulating genes and immune func-tion.

> A more nuanced understanding of

> vitamin E's various functions is needed,

> conference participants said, to deter-mine

> the most useful approaches in us-

> ing this substance to maintain health

> and combat disease.

> HEART HEALTHY?

> Perhaps one of the most perplexing

> questions surrounding vitamin E is its

> role in cardiovascular disease. Oxida-tive

> modification of low-density lipo-protein

> cholesterol is considered a key

> step in the initiation and progression

> of atherosclerosis. Antioxidants such as

> vitamin E have been studied to deter-mine

> their ability to modulate such oxi-dative

> damage and thereby decrease the

> risk of heart disease.

> But as J. Gaziano, MD, MPH,

> of the Brigham and Women's Hospi-tal,

> Boston, pointed out, the vitamin E

> story is " a little unusual in epidemiol-ogy. "

> While the basic science litera-ture

> suggests plausible mechanisms by

> which vitamin E can reduce athero-sclerotic

> events and observational stud-ies

> support this association, results from

> clinical trials have been conflicting in

> that some have shown a clinical ben-efit

> (Lancet. 1996;347:781-786) while

> others have not (Lancet. 1999;354:447-

> 455; N Engl J Med. 2000;342:154-

> 160). A recent meta-analysis of 7 ran-domized

> trials of antioxidant vitamins

> for the prevention of cardiovascular dis-ease

> concluded that the data at this time

> do not support the routine use of vita-min

> E supplements for this purpose

> (Lancet. 2003;361:2017-2023).

> Researchers at the conference pointed

> out that the clinical trials differed from

> each other in a number of important as-pects,

> such as selection of subjects, stage

> of disease, end points, dosage, and

> source of the vitamin—differences that

> have contributed to the inconsistent

> findings and that make the trials diffi-cult

> to compare. Future trials that ad-dress

> these limitations should help pro-vide

> a clearer picture of vitamin E's role

> in cardiovascular disease.

> Another important issue, said Fran-cesco

> Violi, MD, of the Universita La

> Sapienza, Rome, is that not all pa-tients

> at risk for cardiovascular dis-ease

> have high levels of oxidative stress,

> but no trial took this into account.

> Therefore, said Violi, a more targeted

> approach would be to include only pa-tients

> with enhanced levels of oxida-tive

> stress and low vitamin E plasma lev-els

> in order to study those most likely

> to benefit from antioxidant treatment.

> BEYOND alpha-TOCOPHEROL

> Most clinical trials designed to exam-ine

> the ability of vitamin E to prevent

> disease have included the form of vi-tamin

> E called alpha-tocopherol, the most

> abundant form of the vitamin and the

> primary compound used in dietary

> supplements. But recent molecular and

> epidemiological studies have prompted

> researchers to look beyond alpha-tocoph-erol

> to the other forms of vitamin E such

> as gamma-tocopherol.

> Naturally occurring vitamin E is ac-tually

> a complex of 8 chemical com-pounds:

> 4 tocopherols (alpha, beta, gamma, and delta)

> and 4 tocotrienols (alpha, beta, gamma, and delta).

> While gamma-tocopherol (found in corn, soy-bean,

> and sesame oils and walnuts, pea-nuts

> and pecans) is the most common

> form of vitamin E in the US diet, gamma-to-copherol

> levels are generally 10 times

> lower than levels of alpha-tocopherol in

> plasma. For this and other reasons, sci-entists

> have placed a greater focus on

> alpha-tocopherol

> Until recently, that is. Cancer re-searchers

> in particular have begun to pay

> closer attention to gamma-tocopherol. Inter-est

> is shifting to the gamma compound in part

> because results from a number of large,

> prospective studies examining the pre-ventive

> effects of alpha-tocopherol on can-cer

> have been inconsistent. However, it

> should be noted that one study did show

> an association of alpha-tocopherol with a

> reduced incidence of prostate cancer

> (J Natl Cancer Inst. 1998;90:440-446).

> These results will be explored further in

> the Selenium and Vitamin E Cancer Pre-vention

> Trial (SELECT), a large, pro-spective

> trial of selenium and alpha-tocoph-erol

> in more than 30000 men (

> http://www.nci.nih.gov/select ).

> But could alpha-tocopherol be even more

> effective when paired with the gamma com-pound?

> A recent study showed that in-creased

> levels of gamma-tocopherol were as-sociated

> with a significantly reduced

> risk of prostate cancer ( J Natl Cancer

> Inst. 2000;92:2018-2023). The research-ers

> also found that protective effects of

> high concentrations of selenium and

> alpha-tocopherol were only observed when

> gamma-tocopherol concentrations were high.

> This study and others are raising ques-tions

> about gamma-tocopherol's effects on

> other types of cancer.

> COLON CANCER CONNECTION

> Stone, PhD, of East Tennes-see

> State University, City, and

> colleagues are investigating whether

> gamma-tocopherol can inhibit the growth of

> colon cancer. He hypothesizes that in-tracellular

> levels of vitamin E are more

> important than plasma levels in pro-tecting

> cells against the molecular

> mechanisms that can lead to cancer.

> Part of the rationale for his work

> with gamma-tocopherol is that this com-pound

> is taken up by colon cancer

> cells much more effectively than

> alpha-tocopherol. And when alpha- and

> gamma-tocopherol are taken up together

> into cells, the presence of gamma-tocopherol

> increases the level of alpha-tocopherol.

> These findings, said Stone, raise the

> issue " of whether we can really think

> of alpha- and gamma-tocopherol as separate, if

> one influences the absorption of the

> other. "

> In addition, said Stone, gamma-tocoph-erol

> has some unique properties that

> alpha-tocopherol does not have, includ-ing

> the ability to reduce nitrogen diox-ide

> to antioxidant nitric oxide, along

> with the ability to suppress the expres-sion

> of the ras-p21 gene, which en-codes

> a protein known to promote

> oncogenesis.

> In a study done in rats, Stone and col-leagues

> found that gamma-tocopherol plays

> a significant role in providing antioxi-dant

> protection to the epithelial cells of

> the colon and to fecal material (possi-bly

> decreasing the production of mu-tagens

> from the oxidation of fecal

> lipids). In addition, they found that

> expression of the cancer-promoting

> gene ras-p21 was decreased by gamma-tocopherol,

> but not alpha-tocopherol (Can-cer

> Detect Prev. 2002;26:78-84).

> Stone's group also examined the in-fluence

> of gamma-tocopherol on the expres-sion

> of another gene, peroxisome pro-liferator

> activated receptor-gamma (PPAR-gamma),

> a promising target for colon cancer pre-vention.

> Activation of PPAR-gamma with

> drugs such as troglitazone can reduce

> tumor growth by inhibiting cellular pro-liferation

> and inducing programmed

> cell death, or apoptosis, said Stone.

> Because vitamin E possesses struc-tural

> similarities to troglitazone, Stone's

> group wanted to determine whether

> vitamin E could also regulate PPAR-gamma.

> In colon cancer cell studies, they found

> that while both gamma- and alpha-tocopherol

> could upregulate PPAR-gamma protein ex-pression

> (produce more of the protein),

> gamma-tocopherol was much better at this

> task than its alpha cousin (BMC Cancer.

> 2003;3:25). The effect, suggested Stone,

> might be due to the ability of gamma-tocoph-erol

> to accumulate at higher concen-trations

> in colon cells.

> TOCOTRIENOLS AND BREAST CANCER

> Yet another form of vitamin E may be

> a better preventive agent than alpha-to-copherol

> in stemming breast cancer

> growth. Tocotrienols, the major vita-min

> E components in palm oil, seem

> to be the more promising compounds

> in breast tumors, said Kalanithi

> Nesaretnam, PhD, of the Malaysian

> Palm Oil Board, Kuala Lumpur. She

> noted that the body naturally concen-trates

> these compounds in adipose tis-sue,

> the main type of tissue that con-stitutes

> the breast.

> Nesaretnam and colleagues have

> demonstrated in cell culture and ani-mal

> studies the ability of tocotrienols—

> primarily the gamma and delta versions—to in-hibit

> breast cancer cell growth in both

> estrogen-dependent and estrogen-independent

> cells (Lipids. 1998;33:461-

> 469). Apoptosis is one of the mecha-nisms

> by which tocotrienols may inhibit

> tumor growth (Nutr Cancer. 1999;33:

> 26-32).

> Nesaretnam pointed out that that

> alpha-tocopherol has been shown in some

> studies to inhibit breast cancer cell

> growth, but cell culture studies show in-hibiting

> cancer cell growth requires

> much higher levels of alpha-tocopherol than

> of tocotrienols. (She noted that the form

> of alpha-tocopherol that brought about in-hibition

> in breast cancer cell lines is alpha-tocopherol

> succinate—not alpha-tocoph-erol

> acetate, which is what is found in

> most commercial preparations of vita-min

> E.) In addition, although alpha-tocoph-erol

> succinate has been shown to achieve

> inhibition of tumor growth in vivo, this

> is seen only when the compound is in-jected

> into the tumor. In contrast, her

> group has found that tocotrienols taken

> orally suppress breast tumor growth in

> mice (Lipids. 2002;37:557-560).

> Tocotrienols have been shown to po-tentiate

> the antiproliferative effects of

> tamoxifen in both estrogen-depen-dent

> and estrogen-independent breast

> cancer cells in culture. Using this as a

> rationale, Nesaretnam and colleagues

> have begun a clinical trial in Kuala

> Lumpur to look at the effects of tocot-rienols

> in combination with tamoxi-fen

> in 240 women with stage 1 or 2 es-trogen-

> dependent breast cancer. The

> end points will be recurrence of dis-ease

> and metastasis.

> Using microarray technology to study

> the specific genes regulated in breast

> cancer cells by tocotrienols, Nesaret-nam's

> group has identified a few genes

> involved in inhibiting cell growth and

> differentiation. These results suggest

> that tocotrienols affect cell homeosta-sis

> independently of their antioxidant

> activity, she said.

> NEW HORIZONS

> While research continues into the

> antioxidant actions of vitamin E, the

> vitamin's nonantioxidant functions

> are beginning to steal the spotlight,

> said, Lester Packer, PhD, of the Uni-versity

> of Southern California, Los

> Angeles, one of the conference's orga-nizers.

> In addition, vitamin E shows

> promise in illnesses ranging from Alz-heimer

> disease, preeclampsia, and

> upper respiratory tract infections in

> the elderly.

> " Whole new approaches to under-standing

> vitamin E in biological sys-tems

> and in health and aging have

> arisen in recent years, " he said. The

> hope, said Packer and other experts, is

> that such approaches will provide in-sights

> that will open up new avenues

> of research and lead to tangible ben-efits

> for patients.

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